Type 2 diabetes mellitus continues to pose a substantial global health burden due to its rising prevalence and complex metabolic nature. Multifactorial defects, including insulin resistance, β-cell dysfunction, and altered incretin activity, limit the effectiveness of single-target therapies. Current treatment strategies often fail to achieve sustained glycemic control, and delays in treatment intensification persist, highlighting the need for more effective and timely therapeutic approaches. This review evaluates independent and combined therapeutic strategies, focusing on their mechanisms, clinical performance, and applicability in diverse patient populations. A narrative synthesis of recent clinical trials, guidelines, and real-world evidence from 2015 to 2025 was conducted to compare outcomes and identify optimal treatment pathways. Evidence indicates that stepwise approaches remain practical and cost-effective, particularly in early disease stages and resource-limited settings. Early combination strategies demonstrate superior glycemic control, improved durability, and additional cardiovascular and renal benefits. Personalized treatment approaches further enhance outcomes by aligning therapy with individual patient characteristics. This approach underscores the importance of integrating mechanistic understanding with clinical decision-making to enhance therapeutic effectiveness. These findings support a shift toward early, targeted, and individualized interventions to optimize long-term disease management. Integration of combination strategies with patient-centered care models may improve clinical outcomes and reduce complications.
Sambhav et al. (Thu,) studied this question.